Cyclopentadiene Compounds For Use In Bioorthogonal Coupling Reactions
SUMMARY
UCLA researchers from the Department of Chemistry and Biochemistry have discovered a class of novel reagents for bioorthogonal reactions. It is stable, dynamically reactive, and readily accessible.
BACKGROUND
Bioorthogonal reactions link biomolecules to traceable probes that allow studies of biochemical processes in living organisms. These reactions are common practices in many biological applications, such as protein labeling, which is projected to reach a market of $4.2 billion by 2021.
The current golden-standard methods in bioorthogonal cycloadditions are strain-promoted azide alkyne cycloaddition (SPAAC) and the inverse electron-demand tetrazine trans-cyclooctene Diels-Alder reaction. These reactions are rapid, selective and relatively inactive towards other biochemical processes in living cells. Having more reagents that allow biorthogonal reactions like the golden-standards allows diversification of tools and achievable reactions. Nevertheless, researchers are looking to improve reagent stability and selectivity towards sensitive biochemical compounds.
INNOVATION
A class of novel reagents have been reported to facilitate bioorthogonal reactions in complex biological mediums. Cyclopentadiene is a classic diene that can be stabilized with electron donating substitutes. When stabilized, the molecule does not dimerize or come together as a pair, making it “self-orthogonal.” This dramatically increases the speed and efficiency of bioorthogonal reactions when using cyclopentadiene reagents. A particular cyclopentadiene, 6,7,8,9-tetrachloro-1,4-dioxospiro[4,4]nona-6,8-diene (TCK), was described to be highly reactive, self-orthogonal, and ambiphilic. TCK was tested to have great bioorthogonal potential with comparable reaction time to existing bioorthogonal reagents. TCK is also very stable at both room temperature and body temperature in complex biological mediums. It is capable of dual-labeling of biomolecules when used in conjunction with orthogonal bioorthogonal reactions. Furthermore, it is synthesized from cheap and readily available starting materials, making it an ideal candidate for long-term and mass applications of bioorthogonal reactions.
APPLICATIONS
Bioorthogonal coupling reactions:
- Label peptides, glycans, lipids and etc.
- Dual labeling with orthogonal bioorthogonal reactions
ADVANTAGES
- Improved cost efficiency
- Very stable both in storage and in complex biological mediums
- Fast reaction time
- Dynamically reactive (ambiphilic)